Summary of Work: The Environmental Immunology laboratory examines the potential consequences of occupational, accidental or therapeutic exposure to chemicals on the function of the immune system. The ongoing objectives include efforts to: (1) evaluate and characterize the ability of environmental agents or selected therapeutics (e.g. drugs used in the treatment of HIV or AIDS-associated opportunistic infections) to induce alterations in immune function, including immunosuppression, hypersensitivity and autoimmunity, and relate the observed alterations to the organism's ability to resist infectious disease and neoplasia (2) continue to refine and develop assays which examine immunologic endpoints and improve their predictive value for human exposures (3) examine the cellular and molecular mechanisms which lead to alterations in immune responses and (4) to examine the role of inflammatory and growth-promoting cytokines in the development of toxicity and neoplasia in the skin, lung and liver. Specific studies include: (a) characterization of cytokines of importance in arsenic-induced neoplasia in the skin and lung, using rodent and human cell cultures as an in vitro model and the TG.AC transgenic mouse as an in vivo model; (b) examination of the mechanism whereby TCDD alone or in combination with TNF alters the expression of proteins associated with cell death in rodent and human cell lines, and induces hepatotoxicity in exposed mice; (c) quantitation of the expression and secretion of cytokines and immunoglobulins in toxicant-exposed human lymphocytes; (d) extension of the NTP risk assessment data base to evaluate the sensitivity and predictability of extended histopathology in detecting the immunotoxic potential of xenobiotics. Studies investigating the dysregulation of proinflammatory cytokines in the skin by anthralin, an anti-psoriatic drug and the modulation of these effects by anti-oxidants were completed within this time period.